Effects of Zortress® + Tacrolimus vs. Standard Immunosuppression on Progression of Coronary Artery Calcifications and Bone Disease in de Novo Renal Transplant Recipients

Not Applicable

Withdrawn

• Conditions: Renal Transplant
• Interventions: Drug: Zortress® /Everolimus

• Registration Number: NCT01612299
• Lead Sponsor: University of Kentucky

Brief Summary

Primary objectives: A. To evaluate the effect of Zortress® versus standard immunosuppression therapy on progression of CAC as evidenced by changes in Agatston scores from baseline and at 6, and 12 months in renal transplantation patients. B. To investigate progression of CAC in patients undergoing renal transplantation within the study period.

Secondary objectives:

1. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on bone mass as evidenced by changes in quantitative computed tomography (QCT) and dual energy X-ray absorptiometry (DXA).

2. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on activity of bone forming and resorbing cells as evidenced by changes in bone histology.

3. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on biochemical parameters of bone turnover as evidenced by changes in serum Parathyroid Hormone (PTH), Bone-Specific Alkaline Phosphatase (BSAP), Tartrate-Resistant Acid Phosphatase (TRAP), Sclerostin, Receptor Activator of Nuclear factor Kappa B Ligand (RANKL), Osteoprotegerin (OPG), , serum CTX (C-terminal telopeptide of type 1 collagen), and urinary NTX (N-terminal cross link telopeptide).

4. To evaluate in renal transplantation the effect of Zortress® versus standard immunosuppression therapy on cardiovascular events, graft rejection and patient survival.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-05
• Study First Submitted: 2012-05-30
• Study First Submitted QC: 2012-06-01
• Study First Posted: 2012-06-05
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-04
• Last Update Posted: 2017-08-07

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• De novo renal transplant recipients (from deceased or living donors) between 18-70 years of age
• Willingness to participate in the study and comply with study requirements as evidenced by signed IRB-approved informed consent

Enrollment

Exclusion Criteria

• Previous solid organ transplant
• Known hypersensitivity to any of the study drugs, or their class, or to any of their excipients
• Recipients of an investigational drug within 30 days before transplant
• Any abnormal physical or laboratory findings of clinical significance which would interfere with conduct of the study
• Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, or unwilling to use medically approved means of contraception

Randomization Exclusion Criteria:

• Platelet count <75,000/mm
• White blood cell count of < 2,000/mm³
• Hypercholesterolemia (>400 mg/dL) or hypertriglyceridemia (>500 mg/dL) despite lipid-lowering therapy
• Presence of any clinically significant infection requiring IV antibiotics
• Positive serum HCG (women of childbearing potential)
• Spot urine protein to creatinine ratio (UPr/Cr ) ≥ 0.5
• Any biopsy-confirmed acute rejection since transplant
• Baseline CAC score < 100 at baseline reading

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Immunosuppression	Zortress® /Everolimus	Tacrolimus + Myfortic®/Cellcept + Corticosteroids
Zortress®	Zortress® /Everolimus	Tacrolimus + Zortress® + Corticosteroids

Primary Outcome Measures

Name	Time	Method
progression of Coronary Artery Calcification	1 year	The primary outcome of this study is the proportion of pts in the treatment group who experience a 1yr increase of ≥2.5 for the square-root transformed volume indicating CAC progression. Student's Fisher's Exact T-tests will be used to determine progression of CAC score between control \& treatment groups. Secondary objectives 1-3 examine 1yr changes in several measurement outcome variables. Fisher's exact tests \& confidence intervals for the difference in proportions will be used to compare the two groups in terms of cardiovascular events, graft rejection, \& pt survival.

Trial Locations

Locations (1)

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States